Method of inducing vasorelaxation to treat pulmonary hypertension

This invention provides a method of selectively decreasing pulmonary vascular resistance in a subject by administering endobronchially a drug chosen from among cAMP analogs, cGMP analogs, phosphodiesterase inhibitors, nitric oxide precursors, nitric oxide donors, and nitric oxide analogs.

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Claims

1. A method for treating pulmonary hypertension in a subject comprising selectively decreasing pulmonary vascular resistance in the subject which comprises administering endotracheally or endobronchially an effective amount of a drug selected from the group consisting of cyclic nucleotides and phosphodiesterase inhibitors or administering an effective amount of a phosphodiesterase inhibitor by injecting a liquid containing the phosphodiesterase inhibitor via the trachea or a bronchus.

2. The method of claim 1 wherein the ratio of the percent change in systemic vascular resistance to the percent change in the pulmonary vascular resistance is about 0.5 or less.

3. The method of claim 1, wherein the ratio of the percent change in systemic vascular resistance to the percent change in the pulmonary vascular resistance is about 0.3 or less.

4. The method of claim 1 wherein the ratio of the percent change in systemic vascular resistance to the percent change in the pulmonary vascular resistance is about 0.04 or less.

5. The method of claim 1, wherein the subject is a mammal.

6. The method of claim 5 wherein the mammal is a pig.

7. The method of claim 5 wherein the mammal is a human.

8. The method of claim 1, wherein the administering comprises injecting a liquid containing the drug via the trachea or a bronchus.

9. The method of claim 1, wherein the administering comprises inhaling the drug in an aerosol form.

10. The method of claim 9 wherein the aerosol is generated by a nebulizer.

11. The method of claim 9 wherein the aerosolized drug is administered as an aqueous solution.

12. The method of claim 9 wherein the areosolized drug is administered as an micronized power.

13. The method of claim 1, wherein the pulmonary vascular resistance is decreased by at least about twenty-four percent.

14. The method of claim 1, wherein the pulmonary vascular resistance is decreased by up to about sixty-four percent.

15. The method of claim 1, wherein the pulmonary vascular resistance is decreased between about twenty-four percent and about sixty-four percent.

16. The method of claim 1, wherein the pulmonary vascular resistance is decreased for over ninety minutes.

Referenced Cited
U.S. Patent Documents
4623666 November 18, 1986 Kennedy
4956348 September 11, 1990 Gilbard
5175151 December 29, 1992 Afonso et al.
5191084 March 2, 1993 Bagli et al.
5217997 June 8, 1993 Levere et al.
5250700 October 5, 1993 Bagli et al.
5366977 November 22, 1994 Pollard et al.
5370989 December 6, 1994 Stern et al.
5376666 December 27, 1994 Duncia
Other references
  • A.G. Gilman, et al., "Goodman and Gilman's The Pharmacological Basis of Therapeutics" (New York: Macmillan 1980) pp. 592-607. Rossaint, et al., The New England Journal of Medicine (Feb. 11, 1993) 328(6):399-405. Archer, et al., J. Appl. Physiol. (1990) 68(2):735-747. Lawson, et al., presented at American Heart Association Meeting, Atlanta, Georgia, Nov. 8-11, 1993. Brackett et al. Biochemical Pharmacology 39(12): 1897-1904, 1990.
Patent History
Patent number: 5728705
Type: Grant
Filed: Oct 4, 1993
Date of Patent: Mar 17, 1998
Assignee: The Trustees of Columbia University in the City of New York (New York, NY)
Inventors: Charles A. Lawson (Verona, NY), David J. Pinsky (Riverdale, NY), Arthur Smerling (New Rochelle, NY), David M. Stern (Great Neck, NY)
Primary Examiner: Gary L. Kunz
Attorney: John P. White
Application Number: 8/131,984
Classifications
Current U.S. Class: 514/261; Nitrogen Containing Hetero Ring (514/79); Phosphorus Containing (514/48); 536/2611
International Classification: A61K 6170; A61K 3133; C07H 1920; C07D47300;